Integrative analysis of physiological responses to high fat feeding with diffusion tensor images and neurochemical profiles of the mouse brain

Irene Guadilla,Sebastián Cerdán,Blanca Lizarbe,Pilar López-Larrubia,Laura Barrios

doi:10.1038/s41366-021-00775-9

Abstract

BackgroundObesity proceeds with important physiological and microstructural alterations in the brain, but the precise relationships between the diet and feeding status, its physiological responses, and the observed neuroimaging repercussions, remain elusive. Here, we implemented a mouse model of high fat diet (HFD) feeding to explore specific associations between diet, feeding status, phenotypic and endocrine repercussions, and the resulting microstructural and metabolic alterations in the brain, as detected by diffusion tensor imaging (DTI) and neurochemical metabolic profiling.MethodsBrain DTI images were acquired from adult male C57BL6/J mice after 6 weeks of HFD, or standard diet (SD) administrations, both under the fed, and overnight fasted conditions. Metabolomic profiles of the cortex (Ctx), hippocampus (Hipc), and hypothalamus (Hyp) were determined by 1H high-resolution magic angle spinning (HRMAS) spectroscopy, in cerebral biopsies dissected after microwave fixation. Mean diffusivity (MD), fractional anisotropy (FA) maps, and HRMAS profiles were complemented with determinations of phenotypic alterations and plasma levels of appetite-related hormones, measured by indirect calorimetry and multiplex assays, respectively. We used Z-score and alternating least squares scaling (ALSCAL) analysis to investigate specific associations between diet and feeding status, physiological, and imaging parameters.ResultsHFD induced significant increases in body weight and the plasma levels of glucose and fatty acids in the fed and fasted conditions, as well as higher cerebral MD (Ctx, Hipc, Hyp), FA (Hipc), and mobile saturated fatty acids resonances (Ctx, Hipc, Hyp). Z-score and ASLCAL analysis identified the precise associations between physiological and imaging variables.ConclusionsThe present study reveals that diet and feeding conditions elicit prominent effects on specific imaging and spectroscopic parameters of the mouse brain that can be associated to the alterations in phenotypic and endocrine variables. Together, present results disclose a neuro-inflammatory response to HFD, characterized primarily by vasogenic edema and compensatory responses in osmolyte concentrations.

Highlights

Obesity and overweight are thought to develop from unhealthy life style habits, combining the exacerbated consumption of diets rich in fats and sugars with sedentary behaviors [1]
Body weight values measured before Magnetic resonance imaging (MRI) performance (Supplementary information, Table 1) were significantly higher in high fat diet (HFD) mice as compared to standard diet (SD) animals, both in the fed and fasting conditions (Fig. 1B)
Blood glucose levels measured prior to the MRI acquisitions were significantly higher in the fed state of HFD animals (p < 0.05), and decreased upon fasting (p < 0.05) (Fig. 1C) (Supplementary information, Table 1)

Summary

Introduction

Obesity and overweight are thought to develop from unhealthy life style habits, combining the exacerbated consumption of diets rich in fats and sugars with sedentary behaviors [1] These circumstances lead, to impairments in the regulation of the cerebral mechanisms controlling global energy balance and addictive behavior [2], favoring a phletora of life-threatening comorbidities which have reached pandemic proportions worldwide [3, 4]. Considerable evidence accumulated, revealing important morphological and metabolic alterations in the brain of obese individuals, as well as in animal models of obesity These included in general, gray matter reductions [11] and cognitive impairment [12], as well as increases in tricaboxylic acid (TCA) cycle flux, anaplerosis, and GABA production [13, 14]. We implemented a mouse model of high fat diet (HFD) feeding to explore specific associations between diet, feeding status, phenotypic and endocrine repercussions, and the resulting microstructural and metabolic alterations in the brain, as detected by diffusion tensor imaging (DTI) and neurochemical metabolic profiling

Methods

Results

Conclusion